The focus of our SCOR is the interplay between estrogen and parathyroid hormone in both the development and treatment of osteoporosis. This project, which represents the cell biology component, will address significant gaps in our knowledge of how estrogen and PTH affect the recruitment and activity of the osteoclast, a key cell in the pathogenesis of osteoporosis. The project has been designed to gain fundamental information on the hormonal regulation of the osteoclast, information that will underpin the studies proposed in all of the other four projects of this application. While it is common knowledge that estrogen deficiency stimulates bone resorption nd that parathyroid hormone may have both catabolic and anabolic actions on bone, the cellular mechanisms underlying these effects are not well understood. Thus, the project focuses on the effects of estrogen withdrawal, and estrogen and PTH supplementation on osteoclast recruitment and activity. These themes are re-addressed in the animal studies in Projects 2 and 3, allowing links to be forged between the cell biology and the clinical studies proposed in Projects 4 and 5.